We propose to synthesize derivatives of retinal and to study the formation of visual pigments from these analogues both in vitro and in vivo. The chemical models will be selected so as to investigate some steric and/or electronic feature of the binding site in rhodopsin. The compounds will be fully characterized and purified by high pressure liquid chromatography prior to incorporation studies. The in vitro studies will be conducted using opsin isolated from bovine retinae. Standard pigment regeneration methods will be used and all pigments formed will be fully characterized (rates of formation and bleaching, cd and absorption data). Studies of analogue combination with intact skate retinae will also be undertaken. The in vivo studies will be carried out on vitamin A deficient albino rats. Incorporation will be monitored by the return of a visual evoked response. The structural integrity of the incorporated analogue will be determined by extraction of the chromophore in organic solvent from the dissected retina followed by analysis of the extract by high pressure liquid chromatography.